Methods for the selective functionalization of aromatic C—H bonds under mild, neutral conditions have been shown to be useful for a wide range of applications, ranging from material science to medicinal chemistry (Godula, et al., Science 312:67-72 (2006); Lyons, et al., Chem. Rev. 110:1147-1169 (2010); Mkhalid, et al., Chem. Rev. 110:890-931 (2010); and J. F. Hartwig, Acc. Chem. Res. 45:864-873 (2013). Palladium-catalyzed oxidative functionalization of arenes and iridium-catalyzed borylations of arenes are the two classes of arene functionalization reactions most widely used. The palladium-catalyzed oxidative functionalization allows the introduction of a new functional group, usually, at a position ortho to a directing group that can bind to the catalyst (Lyons. et al., Chem. Rev. 110:1147-1169 (2010)). The iridium-catalyzed borylation of arenes generates organoboronate esters in which the most sterically accessible C—H bond of an arene is converted to a carbon-boron bond (Mkhalid, et al., Chem. Rev 110:890-931 (2010)).
A method to form the carbon-silicon bonds in aryl silanes by C—H silylation would be an important class of arene functionalization. This reaction is important to develop because aryl silane derivatives are monomers for copolymerizations that generate silicone materials, and aryl silanes are synthetic intermediates that undergo oxidation, halogenation, and cross coupling as part of the synthesis of complex organic molecules (Fleming, et al., Organic Reactions, A. S. Kende, Ed. (John Wiley & Sons, 1989), Vol. 2, pp. 57-193; Luh, et al., The Chemistry of Organic Silicon Compounds, Y. A. Z. Rappoport. Ed. (John Wiley & Sons, Chichester, 2003), vol. 2). Moreover, this reaction is important to develop because it draws parallels to the borylation of arenes but uses simpler, more accessible, and safer reagents and could lead to regioselectivities that complement those of the borylation of arenes.
Much effort has been spent to develop the silylation of arenes, but this reaction has not been used as a synthetic method. Most intermolecular arene silylations were conducted at high temperatures with a large excess of arenes relative to the silane (Ezbiansky, et al., Organometallics 17:1455-1457 (1998); Ishiyama, et al., Angew. Chem. Int. Ed. 42:5346-5348 (2003); Saiki, et al., Organometallics 25:6068-6073 (2006); Murata, et al., Chem. Lett. 36:910-911 (2007); Sakakura, et al., Chem. Lett. 16:2375-2378 (1987); and Ishikawa, et al., Organometallics 11:4135-4139 (1992)), and most arenes that would be used as reagents for synthetic purposes are the more valuable of the two reactants. Some examples were also conducted with disilanes that require a multi-step synthesis (Ishiyama, et al., Angew. Chem. Int. Ed. 42:5346-5348 (2003); Saiki, et al., Organometallics 25:6068-6073 (2006)). In other cases, triethylsilane has been used as the silicon reagent for the functionalization of arenes and heteroarenes (Ezbiansky, et al., Organometallics 17:1455-1457 (1998); Sakakura, et al., Chem. Lett. 16:2375-2378 (1987); and Lu, et al., Angew. Chem. Int. Ed. 47:7508-7510 (2008)). Although triethylsilane is an inexpensive reagent, the coupling of an arene with a trialkylsilane has limited potentials in addressing synthetic problems because the aryl trialkylsilanes do not undergo oxidation or cross-coupling. For such applications, at least one group that is bound to silicon through a heteroatom or bound to silicon by carbon, but cleavage by fluoride or other additive is needed.
Several groups have reported intramolecular or directed silylation of aryl and alkyl C—H bonds (Ihara. et al., J. Am. Chem. Soc. 131:7502-7503 (2009); Kakiuchi, et al., Chem. Lett. 30:422-423 (2001); Oyamada, et al., Angew. Chem. Int. Ed. 50, 10720-10723 (2011); Williams, et al., J. Chem. Soc., Chem. Commun., 1129-1130 (1995); Ureshino, et al., J. Am. Chem. Soc. 132:14324-14326 (2010); Kuninobu, et al., Org. Lett. 15:426-428 (2013); Simmons, et al., J. Am. Chem. Soc. 132:17092-17095 (2010); Simmons, et al., Nature 483:70-73 (2012); and Choi, et al., J. Am. Chem. Soc. ASAP, (2013)), a subset of which is beginning to be used in synthetic applications. For example, imines (Williams, et al., J. Chem. Soc., Chem. Commun., 1129-1130 (1995)), pyrazoles (Ihara, et al., J. Am. Chem. Soc. 131:7502-7503 (2009)), methoxy (Oyamada, et al. Angew. Chem. Int. Ed. 50, 10720-10723 (2011)), and pyridine (Choi, et al., J. Am. Chem. Soc. ASAP (2013)) groups have been shown to bind to platinum, ruthenium, scandium, and iridium catalysts, respectively, to promote silylation ortho to the directing groups. Though the intramolecular silylation of sp2 and sp3 C—H bonds with (hydrido)silyl ether has been demonstrated in the presence of a iridium catalyst (Simmons, et al., J. Am. Chem. Soc. 132:17092-17095 (2010); Simmons, et al., Nature 483:70-73 (2012)), these catalysts have not led to the intermolecular silylation of arene C—H bonds with the arene as limiting reagent.
A synthetic reaction mixture with components of use to silylate an arene moiety and methods of using such a reaction mixture to form silyl arenes would represent a significant advance in synthesizing silyl arenes. The present invention provides such reaction mixtures and methods.